Noninvasive prenatal testing in the general obstetric population: clinical performance and counseling considerations in over 85,000 cases.

ObjectiveThe primary goal of this study was to provide clinically relevant information for appropriate patient counseling. MethodDemographics and test metrics were reviewed for 86658 clinical cases. Outcome information was requested for samples reported as aneuploidy detected or suspected for chromosomes 21, 18, or 13; voluntary outcome reporting was encouraged for all discordant outcomes. ResultsOf 86658 cases, 85298 (98.4%) met inclusion criteria for result reporting. Of the 1360 (1.6%) cancellations, only 101 (0.1%) were for technical reasons. Average time to result was 3.3 business days. Aneuploidy was detected or suspected in 2142 (2.5%) samples. For aneuploidy detected cases with known clinical outcomes, the overall positive predictive value (PPV) was 83.5% (608/728); observed PPVs for trisomies 21, 18, and 13 ranged from 50.0 to 92.8%. As individual PPVs are determined by a patient's prior risk, we developed a chart for counseling patients on positive predictive value based on maternal age. ConclusionThis large-scale report reinforces that noninvasive prenatal testing is a highly accurate screen for fetal aneuploidy in the general obstetric population. Test improvements have facilitated a reduction in failure rates, time to result, and borderline results/unclassifiable results. We have developed a positive predictive value counseling tool to ensure appropriate patient education, counseling, and clinical utilization. (c) 2015 Illumina. Prenatal Diagnosis published by John Wiley & Sons, Ltd. What's already known about this topic? Noninvasive prenatal testing (NIPT) has been shown to screen for common fetal aneuploidies with high sensitivity and low false positive rates. NIPT is a reliable alternative to current fetal aneuploidy serum screening methods in the first and second trimesters. Previous publications detailing NIPT clinical experience have shown that NIPT is performing as well as it performed in clinical validation studies. What does this study add? Analysis of over 85 000 samples submitted to the clinical laboratory suggests that whole genome sequencing-based NIPT continues to meet or exceed performance characteristics established by clinical validation studies for screening of fetal aneuploidy. A tool to guide appropriate pre-test and post-test counseling of patients on estimated positive predictive values based on their personal maternal-age based risk, with recommendations for effective implementation into clinical practice.